Streptococcus pneumoniae is a major cause of morbidity and mortality;pneumococcal polysaccharide vaccination (PPV) to prevent invasive pneumococcal disease (IPD) has been recommended for all persons aged >65 and for younger persons with comorbidities. However, IPD prevention is less than optimal, due in part to infections in persons without vaccine indication and waning immunity after PPV. Recent changes in pneumococcal serotype epidemiology resulting from the childhood pneumococcal conjugate vaccine (PCV) further complicate vaccine policy decision making. IPD due to PCV-related pneumococcal serotypes has significantly decreased in adults but much less so in those with comorbid conditions, prompting investigation of other vaccination strategies, including PPV every 10-15 years and the addition of adult PCV. Clinical trials testing multiple vaccination regiments would be difficult, expensive, and perhaps unhelpful, given rapid epidemiologic changes. Modeling techniques, synthesizing existing data and projecting likely future scenarios could be useful in determining vaccination strategy feasibility and pointing out areas of uncertainty where further data collection would be most valuable. To this end, we propose to: 1) forecast changes in adult pneumococcal serotype epidemiology resulting from childhood PCV using an infectious disease transmission dynamic model and 2) calculate the effectiveness and cost-effectiveness of alternative adult pneumococcal vaccination strategies incorporating forecasted PCV epidemiologic effects. Areas of data uncertainty will be fully incorporated in the model using recently developed analytic frameworks, which will allow probabilistic representation of results and, through value of information analysis techniques, provide evidence-based guidance for optimal future research resource allocation. PUBLIC HEALTH RELEVANCE Disease due to Streptococcus pneumoniae continues to be a significant public health issue, and improvements in preventive strategies are needed. This research will produce a mathematical model to assist pneumococcal vaccine policymaking, particularly in prioritizing and allocating resources to future research efforts.